Hepatocellular carcinoma (HCC) is often diagnosed at the unresectable stage with limited treatment options.1 Immunotherapy with immune checkpoint blockade (ICB) has been shown to provide significant survival benefit for HCC patients with advanced disease. Two combination therapies of anti-PD-L1 plus anti-VEGF or anti-PD1 plus anti-CTLA4 represent the current first-line treatments for unresectable HCC.2 3 However, only about one-third of patients respond to therapy, typically in the context of immune-enriched (‘hot’) tumour microenvironments.4 5 Therefore, there is a major need for treatment strategies that overcome ICB resistance. In Gut, Tu et al observe a correlation of poor prognostic outcomes by anti-PD-1-treated patients with high expression of major histone deacetylases (HDACs) by HCC tumours.6 They, therefore, test the potential of epigenetic immunotherapy combining HDAC inhibitors with ICB therapy in preclinical animal models and provide evidence that the epigenetic immunotherapy…
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Maintenance with niraparib in patients with stage III, stage IV, chemo-naïve recurrent or platinum-sensitive recurrent uterine serous carcinoma: study protocol for a phase II clinical trial
Introduction
Uterine serous carcinoma (USC) accounts for 40% of endometrial cancer-related deaths. The standard of care for stages III and IV USC yields a 20%–30% survival at 2 years and a 10%–20% survival at 3–5 years. Recent advances in the second-line treatment of advanced or recurrent USC are rapidly evolving. Targeted therapeutic approaches with the use of lenvatinib plus pembrolizumab, as well as the use of trastuzumab deruxtecan, offer new hope for successful second-line therapies for patients. However, further investigation into novel targeted therapeutic approaches is warranted, given the high burden of disease associated with this aggressive histological subtype. USC shares clinical and genomic similarities with epithelial ovarian cancer, suggesting a correlation with ‘BRCAness’. Niraparib, a potent PARP1 and PARP2 inhibitor, was shown to have a positive impact on platinum-sensitive recurrent ovarian cancer, regardless of the presence or absence of BRCA status. Our hypothesis is that patients with stage III, stage IV and platinum-sensitive recurrent USC receiving niraparib maintenance in addition to standard therapy for USC may have an improved progression-free survival.
Methods and analysis
Participating sites include the primary site, Northwell Health Zucker Cancer Centre, and secondary site, Rutgers Cancer Institute of NJ. Females over the age of 18 with stage III, stage IV or platinum-sensitive recurrent USC will be recruited and enrolled based on inclusion/exclusion criteria. 24 subjects will be enrolled during phase 1 and 21 subjects will be enrolled during phase 2, over a total of 3 years. Patients will receive an individualised dose of niraparib daily every 28 days per cycle for 1 year or until progression of disease. Follow-up of disease status will continue for 5 years poststudy treatment. This phase II clinical trial will employ a Simon two-stage minimax design to test the null hypothesis that the 1 year response rate is
Neoadjuvant chemotherapy or chemoradiotherapy plus sintilimab versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a study protocol of a multicentre, randomised, controlled, phase III trial (SCIENCE study)
Introduction
Oesophageal squamous cell carcinoma (ESCC) is a globally challenging digestive tract malignancy with poor prognosis and limited treatment options. Early-stage ESCC is often asymptomatic, leading to a late-stage diagnosis in many cases. Neoadjuvant therapy combined with surgery is the standard treatment approach for locally advanced ESCC. In recent years, immunotherapy has shown significant efficacy in ESCC. However, various neoadjuvant treatment regimens, including chemotherapy, radiotherapy and immunotherapy, have produced inconsistent outcomes. This study aims to evaluate the efficacy and safety of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) combined with immunotherapy compared with nCRT alone.
Methods and analysis
This is a prospective, multicentre, randomised, controlled phase III trial enrolling 420 patients with locally advanced thoracic ESCC. Patients will be randomly assigned (1:1:1) into three groups: (A) nCT plus sintilimab, (B) nCRT plus sintilimab or (C) nCRT alone. The primary endpoints are pathological complete response and event-free survival. Secondary endpoints include the objective remission rate, disease control rate, R0 resection rate, major pathological remission rate, disease-free survival, overall survival, patient quality of life and patient-reported outcomes. Data will be analysed using both the intention-to-treat and per-protocol approaches, with multiple imputation methods for handling missing data.
Ethics and dissemination
The study has been approved by the Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital (approval number: SCCHEC-02-2022-108). Written informed consent will be obtained from all participants. The findings will be disseminated through peer-reviewed journals and conference presentations.
Trial registration number
NCT05244798
Local Control and Extended Survival in Locally Advanced Hepatocellular Carcinoma
To the Editor We read with interest the recent article by Dawson and colleagues. This multicenter, phase 3 study (RTOG 1112) offers robust evidence on stereotactic body radiotherapy (SBRT) followed by sorafenib in the treatment of locally advanced hepatocellular carcinoma (HCC). Although the primary outcome, overall survival (OS), did not demonstrate a statistically significant difference between the SBRT with sorafenib and sorafenib alone groups, a multivariable analysis adjusted for stratification factors revealed a 28% lower mortality risk for the SBRT plus sorafenib group. The study holds positive implications because its enrollment criteria matched radiologists’ clinical practices for treating patients with HCC. Several issues should be considered in designing and conducting future clinical studies in similar contexts.
Local Control and Extended Survival in Locally Advanced Hepatocellular Carcinoma
To the Editor We commend Dawson and colleagues on the completion of the pivotal NRG Oncology/RTOG 1112 phase 3 trial. We emphasize a few considerations critical for the interpretation of this landmark trial.
Risk Factor Number and Recurrence, Metastasis, and Disease-Related Death in Cutaneous Squamous Cell Carcinoma
This cohort study examines how risk factor number is associated with the risk of recurrence, metastasis, and disease-related death in cutaneous squamous cell carcinoma.
Error in Key Points and Table 1
In the Original Investigation titled “Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial,” published online December 19, 2024, and in the February 2025 issue, there were errors in the Key Points and Table 1. In the Key Points Findings section, the percentage of patients with macrovascular invasion was updated to 74%. In Table 1, the values in the HCC volume/liver volume row were updated to percentages. This article was corrected online.
Local Control and Extended Survival in Locally Advanced Hepatocellular Carcinoma—Reply
In Reply Sherry et al and Song et al provide insightful remarks on the NRG/RTOG 1112 clinical trial that strengthen the conclusion regarding stereotactic body radiotherapy (SBRT) being associated with clinically important improvements in overall survival (OS) in patients with hepatocellular carcinoma (HCC). Using an adjusted model specific to phase 3 randomized clinical trials, Sherry et al estimate that the probability that SBRT and sorafenib improves OS was 97%, despite the univariate OS primary analysis with a hazard ratio (HR) of 0.77 (90% CI, 0.59 to 1.01) and 1-sided P value of .06, not meeting the statistically significant threshold. They point out that information provided by a P value of .06 vs .05 is nearly identical because P value is a continuous statistic, not binary. In fact, for the present study, the P value for the univariate OS end point was .055, but was reported as .06, consistent with the journal’s reporting guidelines. In addition to reporting effect sizes and clinical importance of the effect sizes, a consortium of statisticians recommended to “report P values to a single significant figure unless the P value is close to .05, in which case, report to 2 significant figures.” The Lancet requires that all P values should be reported to 2 significant figures, unless P
Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma
New England Journal of Medicine, Ahead of Print.
Linee guida italiane sulle neoplasie dell’utero: endometrio e cervice
La Linea Guida AIOM Tumori dell’Utero ha lo scopo di […]
Interventional arterial chemotherapy versus sorafenib for advanced hepatocellular carcinoma in China: a health economic evaluation of open-label, randomised, phase 3 study
Objectives
This post hoc study aimed to evaluate the cost-effectiveness of hepatic artery infusion chemotherapy (HAIC) with fluorouracil, leucovorin and oxaliplatin (HAIC-FO) compared with sorafenib in patients with advanced hepatocellular carcinoma (HCC). The analysis was conducted from the perspective of Chinese payers.
Design
A cost-effectiveness analysis was performed using a Markov model derived from data obtained in the FOHAIC-1 trial (phase 3 randomised controlled trial; conducted 2017–2020).
Setting
The study was conducted in tertiary care centres in China.
Participants
The study included advanced HCC patients enrolled in the FOHAIC-1 trial. Inclusion criteria followed the trial protocols, with patients stratified by disease severity (including the presence of Vp4 portal vein tumour thrombus (PVTT) and high tumour burden).
Interventions
HAIC-FO (fluorouracil, leucovorin and oxaliplatin) was compared with sorafenib for cost and health outcomes.
Primary outcome measure
The primary outcome was the incremental cost-effectiveness ratio (ICER), calculated as the additional cost per quality-adjusted life year (QALY) gained.
Results
Sorafenib yielded 0.66 QALYs at a cost of $15 011.73, whereas HAIC-FO yielded 1.00 QALY at a cost of $18 470.98. The ICER of HAIC-FO compared with sorafenib was $10 235.56 per QALY, which was below the willingness-to-pay (WTP) threshold of $30 492.00 per QALY. Sensitivity analyses confirmed that HAIC-FO remained cost-effective across variable assumptions, with probabilistic sensitivity analysis showing a 99.9% probability of cost-effectiveness at the WTP threshold. Subgroup analyses demonstrated more favourable ICERs for patients with Vp4 PVTT ($7003.33 per QALY) and those with high tumour burden ($7382.86 per QALY).
Conclusions
HAIC-FO is a more cost-effective treatment for advanced HCC than sorafenib from the Chinese payer’s perspective, particularly in patients with Vp4 PVTT and/or high tumour burden. Further research is needed to explore long-term economic implications and real-world effectiveness data.
Trial registration number
NCT03164382.
Relationship of Intra-Pancreatic Fat Deposition With Pancreatic Cancer Differs According to Carcinoma Types
Diagnostic value of BNLF2b antibody, dual-antibody testing and Epstein-Barr virus DNA in nasopharyngeal carcinoma: a prospective cohort study in Hunan Province, China
Objectives
This study evaluates the diagnostic value of the BNLF2b antibody, dual antibody testing and Epstein-Barr virus DNA (EBV-DNA) individually and in combination for nasopharyngeal carcinoma (NPC) detection.
Design
A prospective cohort study.
Setting
The study was conducted at Hunan Cancer Hospital, in a region in China with a high incidence of NPC, between January 2024 and June 2024.
Participants
A total of 350 patients with suspected NPC were enrolled based on clinical suspicion (eg, metastatic cervical lymph nodes or nasopharyngeal abnormalities with non-specific symptoms). The inclusion criteria included age ≥18 years, residency in Hunan Province, and provision of informed consent. The exclusion criteria included prior history of NPC or other head and neck malignancies, severe immunological/systemic diseases and inability to complete diagnostic evaluations.
Primary and secondary outcome measures
Demographic, clinical and biomarker data were collected, including BNLF2b antibody, EBV-DNA and dual antibody testing. Diagnostic performance metrics were calculated against histopathological confirmation as the gold standard. Follow-up assessments were conducted for non-NPC cases.
Results
Among 350 suspected NPC participants, 74 were diagnosed with NPC through biopsy. BNLF2b antibody exhibited the highest sensitivity (83.78%) and specificity (95.65%) among single biomarkers in NPC diagnosis, outperforming dual-antibody testing and EBV-DNA. Combining BNLF2b with dual-antibody testing improved specificity to 99.64%, although with reduced sensitivity (67.57%). NPC-diagnosed participants and those testing positive for BNLF2b or dual antibody biomarkers had a significantly higher prevalence of family history of NPC (p
Mesenchymal intravenous stromal cell infusions in children with recessive dystrophic epidermolysis bullosa: MissionEB protocol for a randomised, double-blinded, placebo-controlled, two-centre, crossover trial with an internal phase I dose de-escalation phase and open-label extension
Introduction
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic mucocutaneous fragility disorder characterised by chronic blistering, slow wound healing and increased risk of squamous cell carcinoma. Current management options are very limited.
Methods
This is a randomised (1:1), placebo-controlled, double-blinded crossover (A/B) trial with an internal phase I dose de-escalation (4+5 design) in the first 3 months and a 12-month continued treatment follow-on open-label study if 3-month outcome data from the crossover trial indicate safe and beneficial effects. RDEB is a rare condition, so we expect to recruit a maximum of 36 participants based on feasibility and not formal power considerations. Participants aged >6 months and
Impact of comprehensive genomic profiling and molecular tumour board on costs and access to tailored therapies: real-world observational study
Objective
There is limited evidence on the economic implications of assessing patients’ access to personalised treatments through Comprehensive Genomic Profiling (CGP) and Molecular Tumour Board (MTB), prompting the need to analyse their impact on the cost of the cancer diagnostic journey (from hospital admission to MTB evaluation) and accessibility to personalised therapies.
Design
Retrospective observational cohort.
Setting
Patients discussed from April 2020 to September 2021 by the institutional MTB operating at Fondazione IRCCS Istituto Nazionale Tumori of Milan, an Italian centre of excellence in oncology pertaining to the national health system.
Participants
676 patients focused on: non-small cell lung cancer (NSCLC), cholangiocarcinoma (CCA), pancreatic carcinoma (PC) and gastro-oesophageal carcinoma (GEC). We defined two different scenarios: (1) patients tested with small Next-Generation Sequencing (NGS) panels (≤60 biomarkers) vs (2) patients tested with comprehensive panels ( >60 biomarkers).
Main outcomes and measures
We measured (1) patients’ eligibility to personalised therapies based on genomic data obtained using targeted somatic NGS panels, (2) MTB cost and the overall diagnostic journey cost and (3) the cost to find a patient eligible to access personalised treatments.
Results
Tumour profiling with comprehensive NGS panels improved patients’ eligibility to personalised therapies compared with small panels (NSCLC: 39% comprehensive panel vs 37% small panel; CCA: 43% vs 17%; PC: 35% vs 3%; GEC: 40% vs 0%). The overall diagnostic journey cost per patient was between 3.2K and 7.4K (NSCLC: 7.4K comprehensive panel vs 6.4K small panel; CCA: 4.9K vs 3.7K; PC: 5.8K vs 4.5K; GEC: 4.2K vs 3.2K). MTB discussion accounted for only 2–3% of the diagnostic journey cost per patient (around 113/patient). The cost to find patient eligible for personalised treatments varied significantly according to panel size and tumour setting (NSCLC: 5K comprehensive panel vs 2.8K small panel; CCA: 4.4K vs 4.4K; PC: 5.5K vs 27K; GEC: 5.2K vs not measurable since none of the patients analysed with small NGS panels were eligible).
Conclusions and relevance
MTB discussion of genomic data obtained with NGS comprehensive panels significantly increases patient eligibility to targeted therapies and optimise the cost to find a patient eligible to personalised treatments, mainly for CCA, PC and GEC patients.